9417814 Birchler The white locus of Drosophila melanogaster will be used as a target gene to study the action of trans-acting dosage modifiers and their potential involvement with coordinate gene expression, dosage compensation, aneuploid syndromes, quantitative traits and position effect variegation. As an approach to the ultimate goal, examples of dosage sensitive regulators will be cloned and characterized, interactions between such dosage sensitive regulators and the male specific lethal locus characterized and a search for recessive mutations which modify the white gene will be made. %%% The regulation of gene expression in multicellular organisms is not a simple linear mechanism. A number of different mechanisms have been or are being described . Over the past several years a regulatory network that results in an inverse dosage effect on the expression of the genes which they affect has been analyzed by this laboratory and this analysis will be continued. ***